2. DRUG DEVELOPMENT
Development of a new
therapeutic drug is a complex,
lengthy and expensive process
costs nearly 900 million dollars
and an average of 15 years.
3. THE TWO TRANSLATIONALTHE TWO TRANSLATIONAL
BLOCKSBLOCKS
Basic
Biomedical
Research
Clinical
Science
and
Knowledge
Goal:
Improved
Health
Translation from
basic science to
human studies
Translation of
new knowledge
into clinical practice
6. IND (Investigational New Drug
Application)
FDA's role in the development of a new drug begins
when the drug's sponsor has screened the new
molecule for pharmacological activity and acute toxicity
potential in animals, wants to test its diagnostic or
therapeutic potential in humans
The molecule changes in legal status under the Federal
Food, Drug, and Cosmetic Act and becomes a new
drug subject to specific requirements of the drug
regulatory system
Drug is to be the subjected to an approved marketing
application before it is transported or distributed
across state lines
IND- notice of claimed investigational exemption for a
new drug must be filed with regulatory body
7. TYPES OF INDTYPES OF IND
Investigator IND
o Submitted by a physician who both initiates and conducts an
investigation, and under whose immediate direction the
investigational drug is administered or dispensed.
o Physician might submit a research IND to propose studying an
unapproved drug, or an approved product for a new indication or
in a new patient population
Emergency Use IND
o Allows FDA to authorize use of an experimental drug in an
emergency situation
o Does not allow time for submission of an IND in accordance with
21CFR , Sec. 312.23 or Sec. 312.34
Treatment IND
o Submitted for experimental drugs showing promise in clinical
testing for serious or immediately life-threatening conditions while
the final clinical work is conducted and the FDA review takes place
8. CLASSIFICATION OF INDCLASSIFICATION OF IND
Commercial
o Permits sponsor to collect data on clinical safety and
effectiveness needed for application for marketing in
the form of NDA
Research (non-commercial)
o Permits the sponsor to use drug in research to
obtain advanced scientific knowledge of new drug
o No plan to market the product
9. CONTENT OF INDCONTENT OF IND
In three broad areas:
Animal Pharmacology and Toxicology Studies –
o An assessment as to whether the product is reasonably safe for initial
testing in humans
o Any previous experience with the drug in humans
Manufacturing Information
o composition, manufacturer, stability, and controls used for manufacturing
the drug
Clinical Protocols and Investigator Information
o Commitments to obtain informed consent from the research subjects, to
obtain review of the study by an institutional review board (IRB), and to
adhere to the investigational new drug regulations.
Once the IND is submitted, the sponsor must wait 30 days30 days before
initiating any clinical trials. During this time, FDA has an opportunity
to review the IND for safety to assure that research subjects will not
be subjected to unreasonable risk
10. FORMAT OF INDFORMAT OF IND
A. Cover sheet (Form FDA-1571)
o Name, address, telephone of sponsor
o Identification of phases
o Commitment not to begin CT until IND approval
o Commitment by IRB- Form 56
o Commitment for conducting CT- accordance with regulations
o Name, title – Monitor
o Name, title – person(s) for reviewing
o Name, Address of CRO, if any
o Signature of sponsor
B. Table of contents
C. Introductory statement & general investigational plan
D. Investigators brochure
E. Study protocol
F. Investigator facilities & IRB data
G. Chemistry manufacturing & control data
H. Pharmacology & toxicology data
I. Previous human experience
11. RESOURCES FOR INDRESOURCES FOR IND
APPLICATIONSAPPLICATIONS
• Pre-Investigational New Drug Application (IND) Consultation Pr
o Offered by CDER (Center for Drug Evaluation and Research) to
foster early communications between sponsors and new
drug review divisions in order to provide guidance on the
data necessary to warrant IND submission.
• Guidance Documents for INDs
o documents are prepared for FDA review staff and
applicants/sponsors to provide guidelines to the
processing, content, and evaluation/approval of
applications and also to the design, production,
manufacturing, and testing of regulated products
12. GUIDANCE DOCUMENTSGUIDANCE DOCUMENTS
For the complete list of CDER guidance, please see theFor the complete list of CDER guidance, please see the
Guidance IndexGuidance Index
Safety Reporting Requirements for INDs and BE/BA Studies
CGMP for Phase 1 Investigational Drugs
Exploratory IND Studies
Content and Format of Investigational New Drug Applications (INDs) for Phase 1
Studies of Drugs, Including Well Characterized, Therapeutic, Biotechnology-Derived
Products
Q & A - Content and Format of INDs for Phase 1 Studies of Drugs, Including Well-
Characterized, Therapeutic, Biotechnology-Derived Products
Bioavailability and Bioequivalence Studies for Orally Administered Drug Products
IND Exemptions for Studies of Lawfully Marketed Drug or Biological Products for
the Treatment of Cancer
Guideline for Drug Master Files
A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA)
that may be used to provide confidential detailed information about facilities,
processes, or articles used in the manufacturing, processing, packaging, and storing
of one or more human drugs.
Required Specifications for FDA's IND, NDA, and ANDA Drug Master File Binders
Immunotoxicology Evaluation of Investigational New Drugs
13. LAWS,REGULATIONS, POLICIES,LAWS,REGULATIONS, POLICIES,
PROCEDURESPROCEDURES
The Federal Food, Drug, and Cosmetic Act is the basic
food and drug law of the U.S The law is intended
to assure consumers that foods are pure and
wholesome, safe to eat, and produced under
sanitary conditions; that drugs and devices are safe
and effective for their intended uses; that cosmetics
are safe and made from appropriate ingredients;
and that all labeling and packaging is truthful,
informative, and not deceptive.
14. LAWS,REGULATIONS, POLICIES,LAWS,REGULATIONS, POLICIES,
PROCEDURES Cont…..PROCEDURES Cont…..
Code Of Federal Regulations (CFR)
o The final regulations published in the Federal Register (daily published record of
proposed rules, final rules, meeting notices, etc.) are collected in the CFR.
o The CFR is divided into 50 titles that represent broad areas subject to Federal
regulations.
o The FDA's portion of the CFR interprets the The Federal Food, Drug, and Cosmetic
Act and related statutes. Section 21 of the CFR contains most regulations
pertaining to food and drugs.
21CFR Part 312 Investigational New Drug Application
21CFR Part 314
INDA and NDA Applications for FDA Approval to
Market a New Drug (New Drug Approval)
21CFR Part 316 Orphan Drugs
21CFR Part 58 Good Lab Practice for Nonclinical Laboratory
[Animal] Studies
21CFR Part 50 Protection of Human Subjects
21CFR Part 56 Institutional Review Boards
21CFR Part 201 Drug Labeling
21CFR Part 54 Financial Disclosure by Clinical Investigators
15. LAWS,REGULATIONS, POLICIES,LAWS,REGULATIONS, POLICIES,
PROCEDURES Cont…..PROCEDURES Cont…..
CDER's Manual of Policies and
Procedures (MaPPs)
MaPPS are approved instructions for
internal practices and procedures
followed by CDER staff to help
standardize the new drug review process
and other activities.
17. Guidance for preparation of INDGuidance for preparation of IND
Reference to document:
http://www.fda.gov/cder/regulatory/applicat
ions/ind_page_1.htm
19. NDANDA (New Drug Application)(New Drug Application)
The vehicle through which drug sponsors
formally propose that the regulatory body
approve a new pharmaceutical for sale and
marketing.
Form 44
The data gathered during the animal studies and
human clinical trials of an Investigational new
product become part of the NDA.
20. GOAL OF NDAGOAL OF NDA
Provide enough information to permit FDA reviewers to
establish the following:
Safety & effectiveness of drug?
Benefits overweigh risks?
Is the drug’s proposed labelling (package insert)
appropriate, and what should it contain?
Are the methods used in manufacturing (Good
Manufacturing Practice, GMP) the drug and the controls
used to maintain the drug’s quality adequate to preserve
the drug’s identity, strength, quality, and purity?
Risk Benefit
21. NDA CONTENTSNDA CONTENTS
1. Introduction
o Brief description of the drug and the therapeutic class to which it
belongs
2. Chemical and
pharmaceutical information
3. Animal Pharmacology
4. Animal Toxicology
5. Human/Clinical Pharmacology phase I
6. Therapeutic exploratory trials (Phase II)
7. Therapeutic confirmatory trials (Phase III)
8. Special Studies
o Geriatrics, pediatrics, pregnant or nursing women
9. Regulatory status in other countries
10. Prescribing information
11. Samples and Testing Protocol/s
22. Once the application is submitted, the FDA has 60 days
to conduct a preliminary review which will assess
whether the NDA is "sufficiently complete to permit asufficiently complete to permit a
substantive review”substantive review”
If everything is found to be acceptable, the FDA will
decide if the NDA will get a standard or accelerated
review and communicate the acceptance of the
application and their review choice in another
communication known as the 74-day letter74-day letter
A standard review implies an FDA decision within about
10 months10 months
23. CONTENTS OF ANDACONTENTS OF ANDA
Data for a drug already approved in the countryData for a drug already approved in the country
1. Introduction
2. Chemical and pharmaceutical information
3. Marketing information
4. Special studies conducted with approval of
Licensing Authority
24. REQUIREMENTS FOR SIMILARREQUIREMENTS FOR SIMILAR
PRODUCTSPRODUCTS
GENERIC DRUGS
Drug product that is comparable to any innovator drug
product in dosage form, strength, route of
administration, quality, performance characteristics and
intended use but is produced & distributed without
patent application.
This drug have already been approved via an NDA
submitted by another maker are approved via an
Abbreviated New Drug Application (ANDA), which does
not require all of the clinical trials normally required for a
new drug in an NDA
o No need for preclinical and clinical data
o Bioequivalence
25. REQUIREMENTS FOR SIMILARREQUIREMENTS FOR SIMILAR
PRODUCTS Cont….PRODUCTS Cont….
BIOLOGICS
Biologics such as vaccines and many recombinant
proteins used in medical treatments are generally
approved by FDA via a Biologic License Application
(BLA), rather than an NDA.
Manufacture of biologics is considered to differ
fundamentally from that of less complex chemicals,
requiring a somewhat different approval process.
26. REQUIREMENTS FOR SIMILARREQUIREMENTS FOR SIMILAR
PRODUCTS Cont….PRODUCTS Cont….
MEDICAL DEVICES
Medical devices are approved by a variety of methods depending
on the class of the device
Class I: Devices that do not require premarket approval
Eg; Dental flossEg; Dental floss
A Pre-market Application (PMA) largely equivalent to an NDA is
required for class III devices.These tend to be devices that are
permanently implanted into a human body or may be necessary
to sustain life.
Eg; artificial heartEg; artificial heart
510(k) approval that shows the device is equal to or better than
a predicate device already on the market is required for class II
devices.
Eg;Eg;Diagnostic tests, cardiac catheters, and amalgam alloysDiagnostic tests, cardiac catheters, and amalgam alloys
used to fill cavities, hearing aidsused to fill cavities, hearing aids
27. REQUIREMENTS FOR SIMILARREQUIREMENTS FOR SIMILAR
PRODUCTS Cont….PRODUCTS Cont….
Drugs for life threatening/serious
disease/relevance to India
Clinical and toxicological data may be
abbreviated, deferred or omitted as per the
licensing authority
